Typhoid research has advanced our understanding of the disease and enabled the development of better vaccines. Antibiotics have been beneficial to treat infections, but they only provide a temporary solution before the bacteria evolves ways to sidestep the drugs. The path towards elimination of typhoid must involve an integrated approach, including both vaccines and improvements to water, sanitation, and hygiene. Two licensed vaccines are recommended for those travelling from high resource countries to endemic areas. A vaccination program in typhoid endemic countries will require a vaccine that is effective and suitable for children less than two years of age, allowing delivery through routine childhood immunization programs. Such vaccines are in development, but await prequalification by the World Health Organization (WHO). Additional information on typhoid conjugate vaccines (TCVs) and efforts to accelerate introduction in endemic areas is available on the Take on Typhoid website.
The first typhoid vaccine was developed in 1896. It was an inactivated whole cell vaccine. It conferred good protection, but it was withdrawn from use because it elicited a strong adverse immune reaction in many recipients.
Two typhoid vaccines are globally available, but because they do not give lasting immunity and are not suitable for children less than two years of age, their potential health benefits are limited and they cannot be included in routine childhood vaccination programs. Neither of the current vaccines is routinely used in endemic areas and uptake is low.
A live attenuated vaccine (Ty21a, trade name Vivotif) is administered orally in three or four doses to adults and children over the age of six. The overall protection is only 50 to 70 percent and vaccination should be repeated every five to seven years.
The Vi vaccine (trade names Typhim Vi and Typherix) is given by injection and is composed of purified polysaccharide polymers of the Vi capsule. The Vi vaccine is licensed for children two years of age and older with a booster dose required every two to three years. Protection ranges from 60 to 70 percent, but since it elicits a T-cell independent immune response it does not provide long-term immunological memory and is not effective in children under two years. The vaccination may be less effective in subsequent administrations.
TCVs overcome many shortfalls of the currently available vaccines. TCVs contain purified Vi polysaccharide conjugated to a protein carrier inducing a T-cell dependent immune response. Compared to the currently available vaccines, TCVs have longer-lasting protection, require fewer doses, and are suitable for children less than two years of age, allowing delivery through routine childhood immunization programs. Suitability of TCVs in children under two is important because they are a key demographic affected by typhoid. The WHO Scientific Advisory Group of Experts (SAGE) recently recommended the introduction of TCVs for infants and children.
There are currently four TCVs, each differing in the identity of the protein component. Two TCVs are licensed and used in India and Nepal and several other TCVs are in development. Typbar-TCV, licensed in India, has shown high seroconversion rates in a Phase III clinical trial, including in children as young at six months. Researchers are also developing live oral attenuated vaccines with rationally-designed mutations.
There are currently no vaccines with efficacy against S. Paratyphi A. This is an urgent need as there are high levels of paratyphoid in parts of Asia.
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